Acylated amino diols



Patented Feb. 27, 1951 ACYLATED AMINO DIOLS Louis L. Bambas, Grosse Pointe Woods, Mich., as-

signor to Parke, Davis & Company, Detroit, Mich., a corporation of Michigan I No Drawing.

8 Claims.

This application is a continuation in part of my co-pending application, Serial Number 83,778, filed March 26, 1949, now Patent No. 2,516,098, and the invention relates to new chemical compounds and to chemical methods useful for their synthesis. More particularly, the invention relates to a new class of acylated amino diols and to methods for obtaining these products. The acylated amino diols of the invention can be represented by the following formula,

H NHAcyl where n is 1 or 2 and R is the same or difierent and represents hydrogen, halogen, nitro, lower alkyl or lower alkoxy radicals. The term acyl as used herein includes saturated and unsaturated lower aliphatic acyl, halogen substituted lower aliphatic acyl, carboxy substituted lower aliphatic acyl, cyano substituted lower aliphatic acyl, ether substituted lower aliphatic acyl, ester substituted lower aliphatic acyl, hydroxy substituted lower aliphatic acyl, benzoyl, substituted benzoyl, araliphatic acyl, furoyl, pyridinoyl and the like radicals.

It will be appreciated by those killed in the art that the products and starting materials of the invention can exist iii structural as well as optical isomeric forms. The term structura isomer or form as used herein refers to the cis or trans, that is, the planar relationship of the polar groups on the two asymmetric carbon atoms. To differentiate between these two possible diastereoisomer we will subsequently refer to the cis compounds as the regula (reg) series or form and to the trans diastereoisomers is the pseudo (1,0) series or form. Such cis compounds are products wherein the two most highly polar of the groups on the asymmetric carbon atoms lie on the same side of the plane of the two carbon atoms. Conversely, the trans or pseudo compounds are those wherein the two most highly polar groups lie on opposite sides of the plane of the two carbon atoms.

Both the regular and pseudo forms exist as racemates of the optically active dextro (d) and levo (1-) rotatory isomers as well as in the form of the individual or separated dextro (d) and levo (1) optical isomers.

Because of the difliculty of representing these structural differences in graphic formulae the customary structural formulae will be used in both the specification and claims and a notation Application January 4, 1950, Serial No. 136,835

placed below or to the side of the formula to deer-'- ignate the particular structural and optical configuration of the compound. Where the formula represents the unresolved mixture of the structural and optical isomers the notation unresolved will be used. However, it should be expressly understood that where no notation appears with a structural formula the formula. should be interpreted in its generic sense, that is, as representing the (1) -1p, (d) (1) -reg. or (d) -reg. isomers in separated form as well as the (dl) t or (dl) -reg. optical racemates or the total unresolved mixture of structural and optical isomers. Such a formula does not merely represent the unresolved mixture of isomers.

In accordance with the invention, acylated amino diols of the above general formula are prepared by several different methods. One of these methods comprises reducing acylated amido keto alcohols of the following formula,

I 1 N HAcyl This transformation may be illustrated diagram-r matically as follows:

NHAcyl l Reduction OH NH Acyl C. can be used. However, in order to lessen hydrogenolysis of the product it is preferable to keep the temperature and pressure as low as pos-. sible. A temperature of about 25 to 45 C. and pressure of about 40 to 1000 lbs/sq. in. are usually suflicient to bring about reduction within a rea sonable time and hence are preferred. Some examples of the hydrogenation catalysts which can (7) all be employed are Raney nickel, palladium, F9119. dium oxide, platinum, platinum oxide and the like. Suitable solvents for the reduction include lower aliphatic alcohols and aqueous solutions of the same, lower aliphatic acids, dioxane-water mixtures and the like. When using the nascent hydrogen method of reduction, metals or alloys such as sodium, potassium, calcium, sodium amalgam, potassium amalgam, iron, and the like are caused to react with the solvent used for the reaction to produce hydrogen in the reaction mixture. Some examples of the solvents which may be used are lower aliphatic alcohols such as methanol, ethanol, propanol; lower aliphatic acids, such as acetic acid and aqueous mixtures of either lower aliphatic alcohols or acids; moist dialkyl ethers such as diethyl ether and lower aliphatic alcoholacid-water mixtures. Specific combinations of these metals and solvents which have been found to be particularly effective in bringing about the reduction of the ketonic compounds are sodium, potassium, or calcium and absolute ethanol or methanol: sodiumor potassium amalgam in moist ether, ethanol or acetic acid; and iron in dilute ethanol containing acetic acid. Although either of the foregoing methods of reduction can be used with about equal success in most instances, there are, of course, instances where such methods of reduction cannot be employed. For example, where the product of the invention to be reduced contains a nitro substituent in the phenyl ring, the desired product must be obtained by one of the following methods of preparation.

Th other methods of preparing the products of the invention consist in the acylation of acylamido alkane diols of the following formula,

and the acylation of amino alkane diols of the following formula,

H-H-CHQOH K301 In carrying out the acylation under substantial anhydrous conditions with an acyl anhydride the reaction mixture is heated at about 60 to 135 C. for a short period of time. In most cases the reaction mixture need only be heated for about five to thirty minutes. If desired, the reaction can even be carriedout at lower temperatures by allowing the reaction to proceed for a proportionately longer period of time. In general, however, the reaction is preferably carried out at about 70-100 C. for about one-half hour. When an acyl halide is used as the acylating agent under substantially anhydrous conditions and in the absence of a catalyst, the reaction is carried out at a temperature below about 50 C. As a precaution against side reactions, it is preferable to use only a slight excess of the acyl halide over that required for reaction with the terminal hydroxyl group and, in the necessary instances, the amino group. When an alkaline catalyst is used in conjunction with either an acyl halide or anhydride, the reaction can be carried out at lower temperatures and within a shorter time. In general, the quantity of acylating agent should not be much in excess of that required to react with the terminal hydroxyl group and, where a free amino diol is used as the starting group, with the amino group. The preferred temperature for the reaction ranges from 20-35" C. although the mixture can be heated to as high as 100 C. if desired.

If an alkaline catalyst is employed, the acylation can be carried out using an acyl halide and an aqueous medium at a temperature between about 0 C. and 35 C. As in some of the previously described modifications of the present acylation process, it is preferable to use only a slight excess of the acylating agent over the theoretically required amount. When the acyl groups are of a type which are readily hydrolyzed, such as lower aliphatic acyl groups, the alkaline catalyst should be a relatively weak alkaline substance such as barium carbonate, calcium carbonate, magnesium carbonate, sodium acetate or the like; however, where the acyl groups are of the type more resistant to hydrolysis such as benzoyl or substituted benzoyl radicals, strongly alkaline catalysts such as sodium hydroxide and the like may be employed. Some specific examples of the alkaline materials which may be used in the above described acylation processes are sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium acetate, calcium hydroxide, calcium carbonate, barium carbonate, magnesium carbonate, barium hydroxide, pyridine, triethylamine, quinoline, N-ethyl morpholine, N-methyl piperidine, and the like.

As pointed out above, the amino diols of the invention and their acylated derivatives can exist in structural as well as optical isomeric forms. Where a particular optical isomeric form or optical racemate of one of the two structural forms of these products is desired, it is necessary to separate the unresolved amino diol or acylated amino diol into its two component structural isomers. This is accomplished quite readily and completely by utilization of the difierences in solubility of the two forms in water, organic solvents or in water-organic solvent mixtures. Some of the organic solvents which can be used in this fractional crystallization or solubilization are lower aliphatic alcohols, acetone, chloroform, ethyl acetate and the like. In some cases, the solvent solubility differential of the two forms is not great enough to afford a cleancut separation of the two structural isomers and in these cases it is preferable to convert the isomer mixture of the free amino diol or acylated amino diol into another acylated derivative of the amino diol whose structural isomers differ more markedly in their solubility characteristics. The structural isomers of this new acylated amino diol can then be separated by fractional crystallization and the appropriate structural form of the product so obtained converted either by acylation or hydrolysis to the desired structural form of the free amino diol or acylated amino diol.

Where a particular optical isomer of the amino diol or acylated derivative thereof is desired the corresponding individual regular or pseudo structural form of the 1-naphthy1-2-amin0propane- 1,3-dio1 is resolved into its optical isomers via an optically active acid addition salt. This resolu-- tion which must be carried out on the free amino diol is performed by forming an acid addition salt of the racemic amine with an optically active acid such as (d)-tartaric, (l)-tartaric, (d -mandelic, (l)-mandelic, bromcamphor sulfonic, (l)- bromcamphor sulfonic, (d)-(d)-camphor sulfonic and (D-camphor sulfonic acids, separating the two isomeric salts by recrystallization from a solvent such as a lower aliphatic alcohol or mixtures of the same with water or other organic solammo vents and then regenerating theindividual optical isomers from the separated optically 'active acid addition salts by neutralizing each one separately. when carrying out this resolution it is desirable, but not absolutely necessary, to choose the form of the optically active acid so that the 11 g. of (dl)-ip-l-(4-biphenylyl)-2-amino-} ropane-1,3-diol is heated with an excess of acetic anhydride at 70 C. for fifteen minutes. The reaction mixture is evaporated to dryness in vacuo and the residue is recrystallized from methanol. The white solid thus obtained is (dl)- t-1-(4-biphenylyl) -2-acetamido-3-acetoxypropane-1-ol of the formula. V

(dl)-ll Form Example 2 55 g. of 2-methyl-4-biphenylyl u-p-toluylamido-p-acetoiqrethyl ketone is dissolved in 1 liter of ethanol, and g. of Raney nickel hydrogenation catalyst is added. The mixture is shaken with gaseous hydrogen under about 50 lbs/sq. in. pressure from three to four hours at room temperature. The catalyst is removed by filtration and the filtrate is heated to boiling and mixed with a quarter volume of hot water. The (dl) -\p-1-(2'- methyl-4- biphenylyl) -2- ptol-uylamido- 3- acetoxypropane-l-ol which separates from the cold solution is collected and purified by recrystallization from dilute ethanol. The formula of this product is, r.

. 0 NIL-Pi on (dl)- t Form Example 3 NQO-OcE-tH-cmO-E-cm (dl)- Form Example 4 9 g. of ((11) --1-(4'-nitro-4-biphenylyl) -2- aminopropane-1,3-diol is heated with an excess or dichloroacetic anhydride at w c. mfifteen "minutes. The reaction mixture is evaporated to dryness in vacuo and the residue recrystallized from ethanol. The white crystalline product thus obtained is (dl)- 1- (4'-nitro-4- biphenylyl) 2 dichloroacetamido 3 dichloroacetoxypropane-l-ol or the formula hill-Rextom Example 5 11 g. oi (dl-ip-l-(4'-nitro-4-biphenylyl)-2- aminopropane-lB-diol is heated with an excess of acetic anhydride at 70 C. for fifteen minutes. The reaction mixture is evaporated to dryness in vacuo and the residue is recrystallized from methanol. The white solid thus obtained is (dl) p 1 (4' nitro 4 biphenylyl) 2- acetamido-3-acetoxypropane-1-ol of the formula.

NorOOdn-dn-cmo-o-cm (dl)-# Form Example 6 A mixture consisting of 2.2 moi. (dl)-reg.- 1 (2' methoxy 3 biphenylyl) 2 cyanoacetamidopropane-l,3-diol and 4.4 g. of furoic anhydride in 10 cc. of dry pyr dine is heated.

for one hour on a steam bath. The reaction mixture is diluted with 70 cc. of 2 N hydrochloric acid, the precipitated solid is collected and washed with sodium bicarbonate solution and then with water. Recrystallization from ethyl acetate yields the desired (dl)-reg.-l-(2'-methoxy-3-biphenylyl) -2-cyanoacetamido-3- iuroyloxypropane-l-ol or the formula,

methoxyacetic anhydride is heated at -100 C. for one hour. The solution is diluted with 5 volumes of petroleum ether, the solid product 001- lected and recrystallized from ethanol. The prodnot thus obtained is (dl) --1-(2',4'-dichloro-4- biphenylyl) 2 carbobenzoxylactamido 3- methomacetoxypropane-l-ol of the formula,

0 on mr -tt-dn-cm ceQ-Onmi: H-cmo-E-o mo on,

(dl)-1P Form Nm-OOen-dm-cmo-i-cnch 2.2 g. of the carbobenzoxy derivative prepared above is dissolved in 30 cc. of glacial acetic acid and reduced catalytically in the presence of palladium oxide. The catalyst is removed by filtration, the filtrate evaporated to dryness in vacuo and the residue recrystallized from ethanol to obtain the desired (d1) a 1 (2',4 dichloro- 4 biphenylyl) 2 lactamido 3 methoxyacetoxypropane-l-ol of the formula,

Example 8 26.5 g. of'4'-ethyl-4-biphenylyl a-benzamidofi-benzoyloxyethyl ketone is dissolved in 500 ml. of ethanol and 2.5 g. of Raney nickel hydrogenation catalyst is added. The mixture is shaken with gaseous hydrogen under about 50 lbs/sq;

in. pressure for three to four hours at room temperature. The catalyst is removed by filtration, the filtrate heated to boiling and mixed with a quarter volume of hot water. The (d1) -1//-1-(4- ethyl-i-biphenylyl) 2 benzamido 3-benzoy1- oxypropane-l-ol which separates from the cold solution is collected and purified by recrystallization from ethanol. The formula for this product is,

(GD-1P Form If desired the corresponding (dl) -reg. isomer, which is more soluble, may be recovered from the aqueous ethanol filtrate.

Example 9 8 cc. of phenylacetyl chloride is added in small portions to a suspension of 4.5 g. of (d1) -reg.-1- (2-iodo-4-biphenylyl)-2-aminopropane 1,3-diol in 60 cc. of 1 N sodium hydroxide solution. After a short time the precipitated solid is collected and purified by recrystallization from methanol to obtain the (dl)-reg.-l-(2-iodo-4-bipheny1yl)- 2-phenylacetamido-3-phenylacetoxypropane 1- 01 of the formula,

on NH-C-CHz-O @Oill-JJH-CPhO-C-C HQ [dl] Reg. form Example 10 g. of p-toluyl chloride is added in small portions to a suspension of 5.8 g. of (d1) -reg.-l- (2,4'-dibrom0-4-biphenylyl) 2 nicotinamidopropane-1,3-diol in 25 cc. of 1 N sodium hydroxide solution with shaking. After the odor of p-toluyl chloride has disappeared, the solid product is collected and purified by recrystallization from methanol. The product thus obtained is (d1)-reg.-l(2,4'-dibromo 4 biphenylyl) 2- nicotinamido-3-p-toluyloxypropane-1-ol of the formula,

[dlJ-Reg. form Example 11 ACzHs (dB- b Form Example 12 3 g. of crotonyl chloride is added to a solution of 2.1 g. of (d1) --1-(4-biphenylyl)-2- aminopropane-1,3-diol in 5 cc. of dry pyridine and the mixture is allowed to stand for twentyfour hours. The mixture is diluted with 35 cc. of 2 N hydrochloric acid and the (dl)--l-(4- biphenylyl) 2-crotonylamido-3-crotonyloXypropane-l-ol collected and purified by recrystallization from methanol. The formula of this product is,

' cH-cH-cmo-c-cihcH-cn.

Example 13 A mixture of 2 g. of (l) -reg.-1-(4-biphenylyl)- 2-acetoxyacetamidopropane-1,3-diol and 2.9 g.

of furoic anhydride in 8 cc. of dry pyridine is heated for one hour on a steam bath. The reaction mixture is diluted with 35 cc. of 2 N hydrochloric acid, the precipitated solid collected and washed with sodium bicarbonate solution and then with water. Recrystallization from ethyl acetate yields (l)-reg.-l-(4-biphenylyl)-2- acetoxyacetamido-3-furoyloxypropane-1 01 of the formula,

(I? O OH IIIHCCH;O( JCH (U-Reg. form Example 14 11 g. of 2,3-dimethyl-4-biphenylyl a-propionamido-p-nicotinoyloxyethyl ketone is dissolved in 200 cc. of ethanol and 1 g. of Raney nickel hydrogenation catalyst is added. The mixture is shaken with gaseous hydrogen under about 50 mula or this product is,

assume lhsJsq. in. pressure from three to four hours at room temperature. The catalyst is removed by filtration, the filtrate heated to boiling and mixed with a quarter volume of hot water. The (d1) p 1 (2.3 dimethyl 4 biphenylyD- 2 propionamido 3 nicotinoyloxypropane 19 01 which separates is collected and purified by recrystallization from dilute ethanol. The for- O OH NH-iL-CHr-CH! QQcn-cn-cmo-c Example 5.5 g. of (d1) -1p-l- (4-bipheny1yl) -2-dichlorol0 the reaction mixture is evaporated to dryness in vacuo. The residual (d1). --1-(4-biphenylyl)- -2-benzamido-3-acetoxypropane-l-ol is recrystallized from ethanol-and has the formula,

0 0 ill? 3 3 Lame: 2533! m-EOOi-E-cHA MM-Br mum r E-cn I'HBI 'IOOT HCHO lAiksiinecondense catalyst 0 NHAeyl 0 NH Acyl Acyistiou taci fact- Reduction and Biphenylyl scyismido acylosy kstones lseparation vb fractional crystallization 0H NHAeyl a 0H NH, FirtHI:H-GH:OH ---v Br- 1 JJH-JJH-CEBOH and resolution L T L .1 via optimally active acid isd B-H iiea, i-r s" hho (D-Horm Biphenylyl aeyismido dials Biiihenyiyl amino diols I lN-scylatim acetamidopropane-1,3-dioi is heated at 80' C. for twenty minutes with cc. of acetic anhydride and then the reaction mixture is evaporated to dryness in vacuo. The residual (d1) -41-1-(4-bi-- phenylyl) 2 dichloroacetamido 3 acetoxypropane-l-ol is purified by recrystallization from ethanol. The formula of this product is,

0 on in-Leach OOen-on-cmo4ai-crn (d)-Reg., (Dd-cg. (dhi. m- (l)-& lorm Biphsnyiyl scykmido diois where R and n have the same significance as given above. Where optically active starting materials are desired, the racemic structural forms of the free amino diols are resolved into their optical isomers via an optically active acid addition salt. Optically active acids suitable for this resolution include (d) -tartaric acid or its diacetyl or dibenzoyl derivatives, (d) -camphor sulfonic acid, (d) -bromcamphor sulfonic acid, (d) -mandelic acid and the like. The optically active amino diols so obtained can be used as starting materials, per se, or are converted by acylation as shown above tothe optically active N-acylamido diol starting materials of the invention.

The following examples serve to illustrate the application of this general method of some 01 the specific starting materials used in the fore- (b) 175 g. of the -biphenylyl bromomethyl ketone hexamethylenetetramine complex is added to 200 cc. of concentrated hydrochloric acid in 1 liter of absolute alcohol and the mixture stirred overnight. The insoluble hydrochloride salt of 4-biphenylyl aminomethyl ketone is collected by filtration, washed with a small amount of cold water and dried at room temperature. The formula of this product is,

II @Oc-cnmmnox (c) The 4-biphenylyl aminomethyl ketone hy drochloride prepared in (b) is dissolved in 500 cc. of glacial acetic acid and 300 cc. of acetic anhydride. 150 g. of sodium acetate is added in small portions with stirring. After the addition has been completed the solution is diluted with water and the i-biphenylyl acetamidomethyl ketone which separates collected and recrystallized from methanol; M. P. 154-5 C. The formula 01 this compound is:

(d) 58 g. of 4-biphenylyl acetamidomethyl ketone is mixed with 300 cc. of methanol and 75 cc. of 40% neutral formalin. 2 g. of sodium bicarbonate is added and the mixture stirred at room temperature for about an hour during which time the desired solid product separates. The insoluble 4-biphenylyl-a-acetamido-B-hydroxyethyl ketone of formula,

II o NH-C-CH;

is collected and purified by recrystallization from ethyl acetate;' M. P. 166-7 C.

(e) 50 g. of i-biphenylyl-a-acetamido-fi-hydroxyethyl ketone is mixed with '75 g. of aluminum isopropylate and 1 liter of isopropanol and the mixture heated under reflux for five hours. During the refluxing period the acetone which is formed is distilled off and a stream of nitrogen is passed through the solution. The isopropanol is distilled from the reaction mixture under reduced pressure and the residue treated with about 1 liter of water. The mixture is heated to boiling to insure complete precipitation of the aluminum hydroxide. filtered while hot and the filtrate allowed to cool. The (dl)-\,'/-l-(4- biphenylyl) -2-acetamido-propane-1,3-diol which separates from the cool solution is collected by filtration and purified by recrystallization from 40% ethanol; M. P. ISO-1 C. The formula of this product is,

with a small amount of water.

mtIFtH-cmcm v (dlJ-gb Form If desired, the corresponding (d1) -reg. isomer may be recovered from the aqueous filtrates.

(f) 12 g. of (d1)--1-(4-biphenylyl)-2-acetamidopropane-l,3-diol is heated with 400 cc. of 5% hydrochloric acid for twelve hours. The reaction mixture is cooled and the hydrochloride salt of (d1) -r//-1-(4-biphenylyl) -2-aminopropane- 1,3-diol which separates collected and washed 1 The hydrochloride salt thus obtained is dissolved in water and the solution treated with an excess of ammonium hydroxide. The (d1) --1-(4-biphenylyl) -2-aminopropane-1,3-diol free base which separates is collected and purified by recrystallization from water; M. P. 149-50 C. The formula of this product is,

OH NH:

(dl)-1,!/ Form (g) 3 g. of (d1)--1-(4-biphenylyl)-2-amino..

' propane-1,3-diol is dissolved in a. minimum amount of water containing a small amount of methanol and the resulting solution treated with an aqueous solution containing an equivalent amount of (d)-tartaric acid. The solution is evaporated to dryness in vacuo and the residue fractionally crystallized from a minimum amount of hot methanol. The first isomer to separate from the solution in crystalline form is the (d) -tartaric acid salt of (l)-i,l/-1-(4-biphenylyl)- 2-aminopropane-1,3-diol. The (d)-tartaric acid salt of (d) -\//1-(4-biphenylyl)-2-aminopropane- 1,3-diol is recovered from the filtrates after removal of the salt of the (1) -isomer.

The (d) -tartaric acid salt of (1)-\,l/-1-(4-biphenylyl) 2 aminopropane 1,3 diolobtained above is dissolved in water, the solution made alkaline to pH 9 with sodium hydroxide solution and the precipitated (l) --1-(4-biphenylyl)-2 aminopropane-l,3-diol free base collected. The formula of this product is,

(l) 11/ Form By decomposing the (d)-tartaric acid salt of (d) Il 1 (4 -biphenylyl) -2-aminopropane-1,3- diol in the same manner as described above for the (l) -isomer, one obtains the free base of (d)- t-1-(4-biphenylyl) -2-aminopropane-1,3-diol. In an analogous manner the (d1)v,l1-1-(4-biphenylyl)-2-aminopropane-1,3-diol may be resolved into its isomeric forms via the (d) -camphor sulfonic acid salt. This is accomplished by reacting the optically active acid with the racemic base in butanol or isopropanol and separating the isomers by recrystallization from n-butanol or isopropanol. The salt of the (1) -isomer separates from the solution first.

The biphenylyl a-acylamido-5-acyloxyethyl ketone used as starting material in the practice of this invention may be prepared according to the following examples. For example, 2'-methyl- 4-biphenylyl a-p-toluylamido-fl-acetoxyethyl ketone, the starting material in Example 2', is prepared as follows:

(a) g. of 2'-methyl-4-biphenylyl bromoauaaoo methyl ketone-hexamethylenetetramine complex is added to 1 liter of methanol and 200 cc. of 12 N sulfuric acid and the resulting mixture stirred overnight at room temperature. The insoluble 2'-methyl-4-biphenylyl aminomethyl ketone sulfate is collected, washed with a small amount of water and dried invacuo. The formula of this product is,

o QGE-cnmnmmso.

(c) A mixture consisting of 65 g. of 2-methyl- 4-biphenylyl-p-toluylamidomethyl ketone, 300 cc. of ethanol and 75 cc. of 40% neutral formalin is treated with 2 g. of sodium bicarbonate. The mixture is stirred at 35 C. for about one and onehalf hours, cooled and the insoluble 2-methyl- 4-biphenylyl a- (p-toluylamido) -p-hydroxyethyl ketone collected. This product which has the formula.

is washed with water and dried in vacuo.

(d) g. of 2'-methyl-4-biphenylyl a-(p-toluylamido) -p-hydroxyethyl ketone is heated at about 75 C. for one-half hour with cc. of acetic anhydride and one drop of concentrated sulfuric acid is added to the solution. The mixture is allowed to stand for one-half hour and then is 14 evaporated to dryness in vacuo. The residue which consists of 2'-methyl-4-biphenylyl n-ptoluylamido-fi-acetoxyethyl ketone of the formuis washed with water and purified by recrystallization from ethanol.

Some of the subject matter disclosed but not claimed herein is described and claimed in my copending applications Serial Nos. 136,831, 136,832, 136,833, 136,834, 136,836, 136,837 and 136,838, all filed January 4, 1950 as continuationsin-part of my application Serial No. 83,778, now Patent No. 2,516,098.

What I claim is:

1. A compound of formula,

0H NHAcyl where n is one of the integers 1 and 2 and R is a member of the class consisting of hydrogen, halogen, N02, lower alkyl and lower alkoxy radicals.

2. A compound of formula,

OH NH Acyl OO-cE-cH-CHm ic 3. (dl) p 1 (4 biphenylyl) -2-acetamido-3- acetoxypropane-l-ol.

4. (dl) p 1 (4 biphenylyl) -2-dichloroacetamide-3-acetoxypropane-1-ol.

5. (dl) p 1 (4 biphenylyl) -2-benzamido-3- acetoxypropane-l-ol.

6. A compound of formula,

NoO-OorkoH-omo Acyl 7. (dl) \l/ 1 (4'-nitro-4-biphenylyl) -2-acetamido-3-acetoxypropane-1-ol.

8. (dl) --l-(4'-nitro-4-biphenylyl) -2- dlchloroacetamido-Zi-acetoxypropane-l-ol.

LOUIS L. BAMBAS.

No references cited. 

1. A COMPOUND OF FORMULA, 